Why Does an Aging Smoker's Lung Develop Idiopathic Pulmonary Fibrosis and Not Chronic Obstructive Pulmonary Disease?

The histopathological pattern is characterized by temporal and spatial heterogeneity with areas of normal-appearing lung parenchyma in close proximity to fibrotic areas with honeycombing, resulting in a marked increase of lung stiffness. [...]whereas emphysema is characterized by destruction of the...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2019-02, Vol.199 (3), p.279-285
Main Authors: Selman, Moisés, Martinez, Fernando J, Pardo, Annie
Format: Article
Language:English
Subjects:
Aging
Cell cycle
Chronic obstructive pulmonary disease
Cigarettes
Deoxyribonucleic acid
Disease
DNA
DNA damage
DNA methylation
Emphysema
Epigenetics
Extracellular matrix
Fibroblasts
Gene expression
Genomes
MicroRNAs
Mutation
Pathogenesis
Pulmonary fibrosis
Senescence
Smoking
Systematic review
Telomerase
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Summary:The histopathological pattern is characterized by temporal and spatial heterogeneity with areas of normal-appearing lung parenchyma in close proximity to fibrotic areas with honeycombing, resulting in a marked increase of lung stiffness. [...]whereas emphysema is characterized by destruction of the interstitial framework and formation of "emphysematous spaces" resulting in increased lung volumes, in IPF, scarring and decreased lung volume are conspicuous features. [...]in-depth profiling of the core lung transcriptome has demonstrated a number of convergent transcriptional regulatory hubs between IPF and COPD (23). In this case, the excessive expression of the canonical WNT pathway also leads to impaired alveolar epithelial cell repair, contributing to the activation of fibroblasts and to extracellular matrix accumulation. [...]quite the opposite to emphysema), in experimental models of lung fibrosis, the genetic or pharmacological inhibition of ß-catenin signaling attenuated the fibrotic response induced by bleomycin (39, 40). [...]comparison of DNA methylation changes in both diseases shows marked differences. miRNAs. miRNAs are endogenous noncoding RNAs that serve as key post-transcriptional regulators in multiple biological processes, whereas their dysregulation is implicated in many diseases.
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.201806-1166PP